Hitherto, for facilitating taking medicines mainly having a strong bitterness and iritative property, gelatin hard capsules have been used. Also, these capsules are generally classified into ordinary gastric hard capsules which are dissolved in a stomach and entero soluble hard capsules which are not dissolved in a stomach but are dissociated in the small intestines. As the enteric capsules, there are known gelatin capsules, the surfaces of the capsules being coated with an alkali-soluble polymer and capsules using an alkali-soluble polymer itself as the base. These capsules utilize the difference in the solubility of the capsules by the difference in pH in the digestive organs. That is, these capsules are not dissolved in a strong acidic stomach having pH of from 1 to 3 but are dissolved in the weak alkaline small intestine such as the intestinum duodenum, the intestinum jejunum, and the intestinum ilium each having ph of from 7.5 to 9.3.
On the other hand, it has been clarified that peptide such as insulin and calcitonin, the absorption of which in digestive organs has been considered to be difficult, is very efficiently absorbed in the large intestine of the colon and the rectum. However, when a peptide preparation encapsulated in ordinary gelatin capsules is simply orally administered, the gelatin capsules are dissolved in a stomach to release the medicament, which is easily decomposed by gastric juices and intestinal protease such as pepsine, trypsin, etc., and loses its effect before reaching the large intestine. Also, even when the medicament is encapsulated in the entero soluble hard capsules as described above, these capsule medicine may pass through a stomach without being dissolved but are relatively easily dissolved in the intestinum duodenum and the small intestine, thereby the medicament is released, the decomposition thereof by intestinal protease can not be avoided, and the effective medical effect can not be expected.
Furthermore, there are similar problems in the medical treatment of a large intestine disease by the PG,4 administration of medicine. For example, for the medical treatment for a ulcerative colitis, 5-aminosalicylic acid or prednisolone is used but when such an anti-inflammatory agent is orally administered in a state of being encapsulated in conventional capsules, the medicament is almost absorbed in the small intestine, thereby a large amount of administration is required for obtaining the medical effect and hence there is a large possibility of causing a side action.
For solving the foregoing problems, it has been desired to develop large intestinal dissociative capsules capable of making local administration of a medicament to the large intestine.